Natural killer (nk) cells and cancernanotechnology-based new methods development for the enhancement of antitumor immunotherapy efficacy

Résumé

It is known that the stimulation of natural killer (NK) and T cells with different cytokines, such as interleukins, enhances their effector functions, which is a reliable strategy for cancer elimination. In this thesis, we present the design and generation of a nanoformulation (IONP@hIL15HIS), based on a biocompatible, biodegradable, and traceable nanomaterial, which activates NK and T cells in vitro, by the presence of interleukin-15 (IL-15) on the surface of the nanoparticle (NP). Importantly, the immobilization of IL-15 on the NP provided this cytokine with certain properties, highlighting, among others, a capacity to lessen the downregulation of homing receptors when T and NK cells are stimulated. Furthermore, two in vivo studies were carried out for two purposes: 1) to model an adoptive cell transfer therapy where IONP@hIL15HIS pre-stimulated human cells were infused in immunodeficient mice (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ) and 2) to evaluate the antitumoral therapeutic effect of IONP@hIL15HIS compared to soluble administration of IL-15 in a melanoma C56BL/6 bearing mouse model. Results showed that mice treated with IONP@hIL15HIS have a tendency to slow tumor growth. Altogether, the results from this thesis are a first step to consider immobilized IL-15 on NPs, i.e. IONP@hIL15HIS, as a new therapeutic tool for cancer treatment